Objective To construct machine learning models based on preoperative inflammatory and radiological features for the prediction of glioma grading and isocitrate dehydrogenase (IDH) mutation status, and to analyze application values of these models and identify the optimal predictive models. Methods A retrospective analysis was conducted on the data of pathologically confirmed glioma patients admitted to Tongji Hospital Affiliated to Tongji University from March 2019 to March 2023. LASSO regression was used to screen feature variables, and predictive models were constructed based on logistic regression (LR), random forest (RF), support vector machine (SVM), gradient boosting decision tree (XGBoost) and K-nearest neighbor (KNN) algorithms. The model performance was comprehensively evaluated using metrics including discrimination ability, area under the precision-recall curve (AUC), accuracy, F1 score and Brier score. The DeLong test was adopted to compare the AUC values among different models; Friedman rank-sum test was used to determine the overall performance differences of the models, with the Nemenyi test applied for multiple comparison correction. Results In the task of glioma grading prediction, the LR model achieved the highest comprehensive score (0.726), and no significant difference was observed between the LR model and the other four models; age was positively correlated with glioma grading (P=0.003). In the task of IDH mutation status prediction, the XGBoost model obtained the highest comprehensive score (0.832), which was superior to the LR (0.762, P=0.035) and KNN models (0.754, P=0.025), while no statistical differences were found between the XGBoost model and the RF or SVM models. Conclusions The LR model for glioma grading prediction and XGBoost model for IDH mutation prediction constructed based on a task-oriented strategy achieve a favorable interpretability while ensuring optimized performance, thereby providing reliable decision support for the individualized diagnosis and treatment of glioma.

OBJECTIVES: Bladder cancer is a common malignancy with high incidence and poor prognosis. N⁶-methyladenosine (m⁶A) modification is widely involved in diverse physiological processes, among which the m⁶A recognition protein YTH N⁶-methyladenosine RNA binding protein F2 (YTHDF2) plays a crucial role in bladder cancer progression. This study aims to elucidate the molecular mechanism by which O-linked N-acetylglucosamine (O-GlcNAc) modification of YTHDF2 regulates its downstream target, period circadian regulator 1 (PER1), thereby promoting bladder cancer cell proliferation. METHODS: Expression of YTHDF2 in bladder cancer was predicted using The Cancer Genome Atlas (TCGA). Twenty paired bladder cancer and adjacent normal tissues were collected at the clinical level. Normal bladder epithelial cells (SV-HUC-1) and bladder cancer cell lines (T24, 5637, EJ-1, SW780, BIU-87) were examined by quantitative real-time PCR (RT-qPCR), Western blotting, and immunohistochemistry for expression of YTHDF2, PER1, and proliferation-related proteins [proliferating cell nuclear antigen (PCNA), minichromosome maintenance complex component 2 (MCM2), Cyclin D1]. YTHDF2 was silenced in 5637 and SW780 cells, and cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), colony formation, and EdU assays. Bioinformatics was used to predict glycosylation sites of YTHDF2, and immunoprecipitation (IP) was performed to detect O-GlcNAc modification levels of YTHDF2 in tissues and cells. Bladder cancer cells were treated with DMSO, OSMI-1 (O-GlcNAc inhibitor), or Thiamet G (O-GlcNAc activator), followed by cycloheximide (CHX), to assess YTHDF2 ubiquitination by IP. YTHDF2 knockdown and Thiamet G treatment were further used to evaluate PER1 mRNA stability, PER1 m⁶A modification, and cell proliferation. TCGA was used to predict PER1 expression in tissues; SRAMP predicted potential PER1 m⁶A sites. Methylated RNA immunoprecipitation (MeRIP) assays measured PER1 m⁶A modification. Finally, the effects of knocking down YTHDF2 and PER1 on 5637 and SW780 cell proliferation were assessed. RESULTS: YTHDF2 expression was significantly upregulated in bladder cancer tissues compared with adjacent tissues (mRNA: 2.5-fold; protein: 2-fold), which O-GlcNAc modification levels increased 3.5-fold (P<0.001). YTHDF2 was upregulated in bladder cancer cell lines, and its knockdown suppressed cell viability (P<0.001), downregulated PCNA, MCM2, and CyclinD1 (all P<0.05), reduced colony numbers 3-fold (P<0.01), and inhibited proliferation. YTHDF2 exhibited elevated O-GlcNAc modification in cancer cells. OSMI-1 reduced YTHDF2 protein stability (P<0.01) and enhanced ubiquitination, while Thiamet G exerted opposite effects (P<0.001). Thiamet G reversed the proliferation-suppressive effects of YTHDF2 knockdown, promoting cell proliferation (P<0.01) and upregulating PCNA, MCM2, and CyclinD1 (all P<0.05). Mechanistically, YTHDF2 targeted PER1 via m⁶A recognition, promoting PER1 mRNA degradation. Rescue experiments showed that PER1 knockdown reversed the inhibitory effect of YTHDF2 knockdown on cell proliferation, upregulated PCNA, MCM2, and Cyclin D1 (all P<0.05), and promoted bladder cancer cell proliferation (P<0.001). CONCLUSIONS O-GlcNAc modification YTHDF2 promotes bladder cancer development by downregulating the tumor suppressor gene PER1 through m⁶A-mediated post-transcriptional regulation.
Humans ; Urinary Bladder Neoplasms/metabolism* ; RNA-Binding Proteins/genetics* ; Cell Proliferation ; Cell Line, Tumor ; Disease Progression ; Acetylglucosamine/metabolism* ; Adenosine/metabolism* ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective To explore the home rehabilitation experience of individuals with fully magnetically levitated left ventricular assist device,and to provide a basis for developing scientific nursing intervention plans and follow-up strategies for clinical practice.Methods Using phenomenological research methods,a semi-structured interview was conducted on 13 patients with fully maglev left ventricular assist device implantation in a tertiary A comprehensive hospital in Wuhan from September to October 2022.Colaizzi's 7-step analysis method was used to analyze the data and extract themes.Results A total of 3 themes and 9 subthemes were extracted,including complex emotions in home rehabilitation(challenges for new characters,anxieties and concerns,regaining new life and full of confidence),difficulties in home self-management(lack of professional knowledge,insufficient exercise,difficulty in managing pump cable bag wounds,weak ability to recognize and respond to external controller alarms),and needs for home rehabilitation(need for continuity of care,desire for more social support).Conclusion Complex emotional experiences and many difficulties and needs exist in the home rehabilitation process of patients after implantation of full magnetic levitation left ventricular assist device.Healthcare professionals should actively pay attention to the postoperative psychological changes of patients,strengthen pre-discharge training to improve patients'self-management ability,and actively build a multi-party Internet home rehabilitation management platform to improve the rehabilitation quality of patients.

[Objective]To explore the academic characteristics and the current status of active inheritance of the acupuncture and moxibustion schools in northern Zhejiang.[Methods]Through literature search,data query,personnel interview and other ways,collect the relevant records of acupuncture and moxibustion in northern Zhejiang,sort out the representative schools and summarize their common academic characteristics.[Results]Upon reviewing the literature,it was discovered that the acupuncture and moxibustion schools in northern Zhejiang had a long and storied history,holding a significant position within the academic system of the"Xiushui medical school".Through historical medical research and interviews,it was summarized that the acupuncture and moxibustion in northern Zhejiang possessed five major academic characteristics:precise acupoint selection,diligent study of classics,skillful application of techniques,compassionate medical practice and emphasis on moxibustion therapy.However,the schools faced challenges such as slow transmission,traditional methods and limited dissemination scope during the process of inheritance.[Conclusion]The acupuncture and moxibustion schools in northern Zhejiang have demonstrated distinct academic characteristics and potential for intergenerational innovation in acupoint theory,manual skills and humanistic care.Their inheritance practices have deepened the academic connotations of the"Xiushui medical school".In the future,it is essential to enhance the current status of active inheritance through modern technology and communication methods to promote the widespread dissemination and sustainable development of the academic ideas of northern Zhejiang acupuncture and moxibustion.

Objective:To investigate the current status of insomnia symptoms and executive function (EF) impairments among adolescents from regions with different economic development levels, and to analyze their relationship with depressive symptoms, so as to provide clues for improved depressive symptoms screening practices.Methods:This population-based cross-sectional study employed a multistage, stratified cluster random sampling method. During November 2017 to January 2018 and December 2018 to January 2019, a total of 2 495 adolescents aged 11 to 18 years were selected from Shanghai, representing a highly developed economic region, and 2 704 adolescents aged 11 to 18 years were selected from Shangrao city, Jiangxi province, representing a less developed economic region. The depressive symptoms were assessed using the short version of the 21-item depression, anxiety, and stress scale, based on which participants were categorized into groups with or without depressive symptoms. Insomnia symptoms and EF impairments were measured using a self-designed insomnia scale and the behavior rating inventory of executive function, respectively. Participants were further classified into 4 subgroups: neither insomnia nor EF impairment, EF impairment only, insomnia only, and comorbid insomnia and EF impairment. Chi-square test was used to compare the differences in basic information of adolescents from different regions. Multivariate Logistic regression models were applied to examine the associations between insomnia, EF impairment, and their combination with depressive symptoms as well as the differences in gender and school-stage among each subgroup.Results:A total of 2 305 adolescents were recruited from Shanghai (1 192 boys and 1 113 girls, 1 266 junior high school students and 1 039 senior high school students) and 2 250 adolescents from Shangrao (1 126 boys and 1 124 girls, 1 146 junior high school students and 1 104 senior high school students). The numbers of adolescents with depressive symptoms, insomnia symptoms and EF impairment in Shanghai were 460 adolescents (20.0%), 907 adolescents (39.3%), and 411 adolescents (17.8%), respectively, all of which were fewer than those in Shangrao, which were 616 adolescents (27.4%), 1 251 adolescents (55.6%), and 524 adolescents (23.3%), respectively (all P<0.001). In Shanghai, the numbers of adolescents with EF impairment only, insomnia only, and comorbid insomnia and EF impairment were 219 adolescents (9.5%), 670 adolescents (29.1%), and 237 adolescents (10.3%), respectively. And in Shangrao, the corresponding numbers were 193 adolescents (8.6%), 865 adolescents (38.4%), and 386 adolescents (17.2%), respectively. Compared to adolescents in Shanghai with neither EF impairment nor insomnia, the risk of depressive symptoms was all higher in adolescents with EF impairment only, insomnia only, and comorbid EF impairment-insomnia ( OR=2.86, 6.48, 20.10; 95% CI 1.57-5.22, 5.09-8.26, 13.66-29.58; all P<0.01). Similar results were observed in adolescents in Shangrao ( OR=3.22, 4.82, 10.91; 95% CI 1.66-6.28, 3.09-7.51, 7.26-16.40; all P<0.01). The analysis of gender and educational stage differences showed that, compared to the group neither EF impairment nor insomnia, the risk of depressive symptoms all higher in the groups with EF impairment only, insomnia only (all P<0.05), and comorbid EF impairment-insomnia, and the risk in comorbid EF impairment-insomnia group was the highest (all P<0.05). Conclusions:Compared with adolescents in regions with underdeveloped economies, those in economically developed regions had lower rates of insomnia, EF impairment, and depression. Both insomnia and EF impairment significantly increase the risk of depressive symptoms. Their coexistence confers the highest risk and therefore warrants particular attention for prevention and intervention efforts.

[Purpose]To analyze the incidence and changing trends of elderly breast cancer(de-fined as diagnosis at age ≥ 60 years old)in China and globally from 1990 to 2021,and to predict its trends from 2022 to 2035.[Methods]Data on the number of new cases and crude incidence rate of elderly breast cancer in China and globally were extracted from the 2021 Global Burden of Disease Study(GBD)database.The age-standardized incidence rate(ASIR)was calculated by sex and age group.The Joinpoint regression model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC),to describe the incidence trend of elderly breast cancer from 1990 to 2021.The Bayesian age-period-cohort(BAPC)model was applied to predict the incidence of elderly breast cancer from 2022 to 2035.[Results]From 1990 to 2021,the number of new breast cancer cases among elderly individuals globally increased from 416 444 to 1 023 776,while in China,the number rose from 26 371 to 158 085.The ASIR increased from 89.04/105 to 94.73/105 globally and from 27.24/105 to 58.40/105 in China.By sex,the ASIR of el-derly females increased from 155.19/105 to 170.54/105 globally and from 49.13/105 to 106.00/105 in China;the ASIR of elderly males increased from 2.78/105 to 4.72/105 globally and from 1.69/105 to 6.81/105 in China.By age group,from 1990 to 2021,the incidence rates of breast cancer in elderly female and male both peaked in the age group of 85～89 years old globally.In China,the most significant increases in incidence rates were observed in the age group of 60～64 years old for elderly females and the age group of 70～74 years old for elderly males;these two age groups had the highest incidence rates in their respective sexes in 2021.Joinpoint analysis showed that the ASIR of elderly breast cancer in China presented a continuous upward trend from 1990 to 2021(AAPC=2.51％),with the fastest growth during 2016-2019(APC=5.14％).The global ASIR showed only a slight fluctuating upward trend(AAPC=0.20％),with significant increases only during 1990-1995 and 2003-2010.Predictions from the BAPC model indicated that by 2035,the global ASIR of elderly breast cancer would reach 107.84/105(192.26/105 for females and 6.02/105 for males),while the ASIR in China would reach 104.35/105(188.08/105 for females and 13.32/105 for males).[Conclusion]From 1990 to 2021,the incidence of elderly breast cancer showed an upward trend both in China and globally,with a particularly pronounced increase in elderly male.The disease burden of elderly breast cancer in China is expected to continue increasing in the future,necessi-tating strengthened primary and secondary prevention measures,as well as optimized screening programs for the elderly population to reduce disease risks and improve prognosis.

Objective To investigate the role and molecular mechanism of SOX4 in Helicobacter pylori(H.pylori)-mediated gastric mucosal epithelial dysplasia.Methods The expression of SOX4 in gastric tissues and cells was analyzed with reverse transcription-polymerase chain reaction(RT-PCR),Western blotting,and immunohistochemical staining.The effects of SOX4 on gastric epithelial cell proliferation and colony formation were determined with CCK-8 and colony formation assays.A PCR array was used to screen downstream target genes involved in H.pylori-induced dysplasia mediated by SOX4.The transcriptional regulation and binding sites of the target gene MLH3 by SOX4 were elucidated with luciferase reporter assay,promoter truncation assay,and chromatin immunoprecipitation(ChIP).Results SOX4 expression was significantly increased in H.pylori-infected gastric tissues(P<0.05).Overexpression of SOX4 markedly enhanced the proliferation and colony formation abilities of normal gastric epithelial cells(P<0.05).Elevated SOX4 led to the dysregulation of MLH3 and other DNA damage repair-related molecules after H.pylori infection in gastric epithelial cells(|logFC|>1,P<0.05).H.pylori promoted MLH3 expression in gastric epithelial cells through SOX4.SOX4 transcriptionally activated MLH3 expression by binding to the 5th site of the MLH3 promoter.The increased expression of SOX4 and MLH3 is associated with poor prognosis of gastric cancer patients.Conclusion SOX4 is closely associated with H.pylori-induced dysplasia in gastric epithelial cells.Upregulation of SOX4 promotes H.pylori-related dysplasia by transcriptionally activating MLH3,leading to the imbalance of proliferation and colony formation in gastric epithelial cells.

Objective:To explore the neuropathological characteristics of brain tissues from autopsy of patients with schizophrenia.Methods:Forty-two autopsy cases from National Human Brain Bank for Health and Disease, School of Medicine, Zhejiang University from January 2013 to December 2024 were selected as research subjects, among which, 21 were schizophrenia patients(schizophrenia group) and 21 were non-schizophrenia patients (non-schizophrenia group). Clinical data of patients from the two groups were compared. HE staining was used to detect the pathological changes such as infarction, hemorrhage and arteriosclerosis in the brain tissues, silver-nitrate staining was used to detect the amyloid plaques in the brain tissues, Congo red staining was used to detect the pathological changes related to cerebral amyloid angiopathy (CAA) in the brain tissues, modified Gallyas silver staining was used to detect the neurofibrillary tangles in the brain tissues, and immunohistochemical staining was used to detect the expressions of phosphorylated tau protein, β-amyloid protein (Aβ), TAR DNA binding protein 43 (TDP-43), and α-synuclein in the brain tissues. Alzheimer's disease neuropathologic change (ADNC), primary age-related tauopathy (PART), limbic-predominant age-related TDP-43 encephalopathy (LATE), aging-related tau astrogliopathy (ARTAG), Lewy body disease (LBD), and cerebrovascular disease (CVD)-related pathological changes in the brain tissues were evaluated, and differences in positive rates of the above pathological changes were compared.Results:No significant difference in gender, age of death, brain weight, or apolipoprotein E genotype was noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Six schizophrenia patients exhibited low-to-intermediate ADNC, including 4 with low ADNC and 2 with intermediate ADNC. Compared with the non-schizophrenia group, the positive rates of ADNC- and CVD-related pathological changes in the schizophrenia group were significantly higher (0 vs. 28.6%; 9.5% vs. 47.6%, P<0.05). No significant differences in positive rates of PART-, LATE-, ARTAG-, and LBD-related pathological changes were noted between the schizophrenia group and non-schizophrenia group ( P>0.05). Conclusion:Schizophrenia patients show high proportions of ADNC- and CVD-related pathological changes, but relatively low ADNC severity.

Objective To explore the value of serum soluble triggering receptor expressed on myeloid cell-1(sTREM-1),interleukin-17(IL-17),and soluble Fas ligand(sFasL)in evaluating severity and prognosis of neonatal infection.Methods From November 2022 to November 2024,a total of 105 neonates with infections who visited the Department of Pediatrics in the hospital were labeled as infection group,and 105 healthy neo-nates were labeled as control group.Based on the severity of neonatal infection,the affected children were as-signed into extremely critical group,critical group,and non critical group.Based on prognosis,the affected children were grouped into adverse group and good group.Enzyme linked immunosorbent assay(ELISA)was used to measured serum sTREM-1,IL-17,and sFasL.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum sTREM-1,IL-17,and sFasL for prognosis.Results The serum levels of sTREM-1,IL-17,and sFasL in the infection group were significantly higher than those in the control group(P＜0.05).The serum sTREM-1,IL-17,and sFasL decreased in serum of extremely critical group,critical group,and non critical group in sequence(P＜0.05).Spearman correlation showed that serum sTREM-1,IL-17,and sFasL levels were positively correlated with disease severity(r=0.601,0.592,0.523,P＜0.05).The proportion of cesarean section,serum levels of sTREM-1,IL-17,and sFasL in the poor group were higher than those in the good group(P＜0.05),and the Apgar score was lower than that in the good group(P＜0.05).Logistic regression revealed that cesarean section,sTREM-1,IL-17,and sFasL were all factors affecting the adverse prognosis of neonatal infections(P＜0.05).ROC curve showed that the area under the curve(AUC)of serum sTREM-1,IL-17,sFasL,and their combined detection in predicting adverse prognosis of neonatal in-fections was 0.781,0.788,0.768,and 0.879,respectively.The AUC of joint prediction was greater than those of individual prediction(Zcombination-sTREM-1=2.238,P=0.025,Zcombination-IL-17=2.014,P=0.044,Zcombination-sFasL=2.248,P=0.025).Conclusion Serum sTREM-1,IL-17,and sFasL levels in neonates with infections are man-ifestly elevated,and they are closely related to the severity and prognosis.